Proliferation index

Elias JM, Rosenberg B, Margiotta M, et al. Antigen restoration of MIB-1 immunoreactivity in breast cancer combined use of enzyme predigestion and low temperature for improved measurement of proliferation indexes. I. Histotechnol. 1999 22 103-106. 

Because MIB-1 monoclonal antibody is used extensively to determine the cell proliferation index, its applications are discussed below. This antibody detects the nuclear antigen Ki-67 expressed in proliferating cells but not in resting cells. The antibody reacts with the nuclei of cells in mid-Gj (first gap), S (DNA synthesis), G2 (second gap), and M (mitosis) phases, but not in the G0 or quiescent phases. The use of MIB-1 antibody is one of the simplest and most reliable labeling techniques for assessing the rate of proliferation of a neoplastic cell population. Thus, the antibody can be used to assess the growth fraction (i.e., the number of cells in cell cycle) of normal, reactive, and neoplastic tissues. 

Comin, C. E., Anichini, C., Boddy, V, Novelli, L., and Dini, S. 2000. MIB-1 proliferation index correlates with survival in pleural malignant mesothelioma. Histopathology 36 26-31. 

Goodson III, W. H., Moore II, D. H., Ljung, B.-M., Chew, K., Florendo, C., Mayall, B., Smith, H. S., and Woldman, F. M. 1998. The functional relationship between in vivo bromodeoxyuri-dine labeling index and Ki-67 proliferation index in human breast cancer. Breast Cancer Res. Treat. 49 155-164. 

Figure 6. Staining obtained with two antibody clones to proliferating cell nuclear antigen (PCNA). Antigen retrieval and staining procedures were identical for the two antibodies, (a) Clone 19A2 showed a proliferating index of 75% compared to (b) to a 98% proliferating index in the adjacent section of breast cancer when stained with clone PC 10.

In most cell populations not all the cells are proliferating, there being a proportion of non-proliferating cells. These may alternatively be described as being in GO or in the A-state. The proliferation index of growth fraction is given by... 

Proliferation Indexes from Repeat-Dose Chronic Toxicity... 

Figure 9.3 Inhibition of intimal hyperplasia by resveratrol in rabbits subjected to endothelial injury by denudation. Groups of eight New Zealand white rabbits, weighting 2.2 to 3.6 kg, were assigned randomly to control (untreated) (M), low (2 mg/kg/d) (L), and high dose (4 mg/kg/d) (H) resveratrol treatment, which was administered intragastrically for 5 weeks beginning 1 week before surgery. A 2-cm segment of injured iliac artery was excised, fixed in 4% paraformalin, embedded in paraffin, and sectioned at5-mm intervals from the proximal to the distal end. Representative sections were stained with hematoxylin/eosin. The external and internal elastic lamina were manually identified. Intimal proliferation index (IPI) was defined as the ratio of intimal area to [intimal+medial] area relative luminal area (RLA) was defined as the ratio of luminal area to [luminal+intimal+medial] area.

Drobnjak, M., Latres, E., Pollack, D., Karpeh, M., Dudas, M., Woodruff, J., Brennan, M., and Cordon-Cardo, C. (1994) Prognostic implications of p53 nuclear overexpression and high proliferation index of Ki-67 and adult soft-tissue sarcomas. J. Natl. Cancer. Inst. 86, 549-554. 

FIG. 3.13. Proliferation index of human peripheral lymphocytes exposed for 1 h to different radioactive concentrations of (a) f IfDOTATATE and (b) LufDOTATATE. No statistically significant differences were observed after the exposures (one way ANOVA, p>0.05). 

The results obtained showed the induction of MN in AR42J cells exposed to 2400 and 5700 kBq/mL of "l.u DOTATATE (Fig. 3.14). The frequency of binucleated cells with MN was 4.0% with exposure to 2400 kBq/mL of I Lu DOTATATE and 5.6% with exposure to 5700 kBq/mL of the radionuclide. Compared with basal values of 2.8% for binucleated cells with MN, there was a 1.4- and 2.0-fold increment, respectively. No alteration of the proliferation index was observed (PI = 1.23). 

The DNA ploidy is expressed by the DNA index (DI). For DI = 1, the DNA is normal and classified as DNA diploid for DI 1, the DNA is abnormal and is classified as DNA aneuploid, a state usually associated with neoplastic cells. On the basis of these parameters, additional parameters for comparative estimation were calculated, including the proliferation index (Pl -SxG x Mf to Gy phase ratios and the coefficient of variation (CV). The normal values... 

For Lu-DOTATATE, multiple dose therapy is more effective than single dose therapy, since a decrease of the tumour proliferation index was observed. The data obtained suggest that optimizing the time interval for multiple dose regimens leads to increases in the therapeutic efficacy. These data show that Lu-DOTATATE could be an effective targeted radiotherapeutic agent. 

In an unadjusted analysis of EFS, patients with intermediate and high risk for relapse had a nearly three- fold increase risk of failure compared to patients in low risk group. Higher levels of IgG antibody to OSM and higher proliferation index to STn were also associated with reduced risks for failure compared to levels lower than the medians. 

Fig. 3. Effect of protein L injection on the proliferation capacity of splenocytes. Transgenic 5-feature mice [46] were injected intraperitoneally with 1 mg of recombinant protein L or the control protein HEL on days 1, 3, 5, 7 and 9. Spleen cells were washed and then cultured at a concentration of 2 X 105 cells in 100 pi in 96-well, round-bottom plates for 18 h in the presence of F(ab )2 anti-human IgM or lipopolysaccharide (LPS). Incorporation of 3H-thymidine was measured and proliferation indexes were calculated. White bars = Control, non-injected mice gray bars = mice injected with HEL black bars = mice injected with protein L. 

Among those, DNA ploidy analysis, proliferation index (Ki-67), and p53 appear to be poised for the earliest transition into the clinical arena. Current research efforts in prostate cancer are also focused on biologic markers that can serve as a target of therapy (Fig. 16.23). 

Ki-67 proliferation index does not reliably distinguish between fibroadenoma and phyllodes tumor. 

Gonzalez-Vela MC, Garijo MF, Fernandez F, et al. MIBl proliferation index in breast infiltrating carcinoma Comparison with other proliferative markers and association with new biological prognostic factors. Histol Histopathol. 2001 16 399-406. 

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